Zhou Mingjing, Wu Wei, Wang Yichang, Zhang Beichen, Zhao Xuyan, Zhou Haoyu, Cao Yiyang, Wu Pancheng, Wang Maode, Wang Jia
Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277, Yanta West Road, Xi'an, Shaanxi, 710061, China.
Center of Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
J Neurooncol. 2025 May 22. doi: 10.1007/s11060-025-05036-7.
As one of the most prevalent primary brain tumors, glioblastoma (GBM) is characterized by its severe malignancy and extremely poor prognosis. Recent studies have demonstrated that targeting anoikis and malignancy showed impressed efficiency for treatment in a wide range of solid tumors, however, relevant research on GBM still remains unclarified.
In this study, genes related with malignancy and anoikis of GBM were identified by utilizing the Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA) and the Molecular Signatures Database (MSigDB). Subsequently, the role of the key gene was validated via proliferation, invasion and migration experiments both in conditions with and without attachment. Moreover, RNA sequencing analysis was employed to reveal further mechanisms.
Here, Type V collagen alpha 1 (COL5A1) was identified as a critical gene associated with anoikis and poor outcomes. Additionally, COL5A1 knockdown induced significant reduction in malignancy of GBM both in vitro and in vivo. Moreover, cell anoikis was remarkable enhanced by reduced expression of COL5A1 after low-attachment cell culture. Mechanically, RNA sequencing analysis revealed that the activity of the Wnt/β-catenin signaling pathway was diminished following COL5A1 knockdown, which indicated that COL5A1 reduced anoikis via regulating Wnt/β-catenin signaling pathway thus promoted malignancies of GBM cells.
These findings demonstrated the novel evidence that COL5A1 serves as an essential regulatory factor influencing both anoikis and malignancy of GBM cells by regulating Wnt/β-catenin signaling pathway, indicating that COL5A1 could be a novel prognosis-related biomarker and potential therapeutic target for GBM.
胶质母细胞瘤（GBM）作为最常见的原发性脑肿瘤之一，具有高度恶性和极差的预后。最近的研究表明，针对失巢凋亡和恶性肿瘤的靶向治疗在多种实体瘤中显示出显著疗效，然而，关于GBM的相关研究仍不明确。
在本研究中，利用癌症基因组图谱（TCGA）、中国胶质瘤基因组图谱（CGGA）和分子特征数据库（MSigDB）鉴定与GBM恶性肿瘤和失巢凋亡相关的基因。随后，通过在有附着和无附着条件下的增殖、侵袭和迁移实验验证关键基因的作用。此外，采用RNA测序分析以揭示进一步的机制。
在此，V型胶原α1（COL5A1）被鉴定为与失巢凋亡和不良预后相关的关键基因。此外，COL5A1基因敲低在体外和体内均显著降低了GBM的恶性程度。而且，在低附着细胞培养后，COL5A1表达降低显著增强了细胞失巢凋亡。从机制上讲，RNA测序分析表明，COL5A1基因敲低后Wnt/β-连环蛋白信号通路的活性降低，这表明COL5A1通过调节Wnt/β-连环蛋白信号通路减少失巢凋亡，从而促进GBM细胞的恶性增殖。
这些发现证明了新的证据，即COL5A1通过调节Wnt/β-连环蛋白信号通路作为影响GBM细胞失巢凋亡和恶性肿瘤的重要调节因子，表明COL5A1可能是GBM一种新的预后相关生物标志物和潜在治疗靶点。
